Milito and Cambiasso out for three weeks
Inter said in a statement on Monday that tests showed striker Milito and midfielder Cambiasso had suffered thigh muscle strains in Argentina's 1-0 defeat in Japan on Friday.
The European champions said their recovery time would be determined in the coming days but similar injuries at the club have taken a little under a month to heal.
If that was the case then both players would miss the Champions League group clash at home to Tottenham Hotspur on October 20 and at least three Serie A matches.
Milito was Inter's top scorer last term and netted the winners when they sealed the scudetto, Italian Cup and Champions League.
The 31-year-old has struggled for form and fitness this term, however, and has been eclipsed by strike partner Samuel Eto'o.
His absence will still be a blow to Rafael Benitez given the coach's limited options, although Goran Pandev is back in training after a knock.
Cambiasso has been one of Inter's most consistent performers for several seasons but his injury coincides with fellow midfielder Thiago Motta returning to full training after knee surgery.
Sulley Muntari has also been little used this term but the Ghanaian has issued a statement denying reports he wants a move.
He left the San Siro before kick-off after being told he was not even on the bench for Inter's 0-0 draw with Juventus last time out.